Preparation of chiral primary amine from asymmetric reductive amination of simple ketone catalyzed by ruthenium-diphosphine catalyst

Abstract

The present invention relates to a preparation method of chiral primary amine. The chiral primary amine is prepared through a one-pot method that under the action of a ruthenium-chiral diphosphine catalyst, a simple ketone and an ammonium salt RCOONH4 have reductive amination by adding hydrogen and then are heated and hydrolyzed by adding acid. The present invention has the advantages of good substrate universality, high reaction efficiency and the like

What is claimed is: 
     
       1. A method for preparing a chiral primary amine, comprising:
 in an argon atmosphere, adding a ketone compound, a ammonium salt, a ruthenium-diphosphine catalyst and an organic solvent to a reaction flask; 
 placing the reaction flask into an autoclave, followed by hydrogen injection, wherein a pressure of the hydrogen is 10-200 atm; 
 performing an oil-bath stirring treatment on the autoclave at 20-160° C. for 0.5-240 h to generate an intermediate; 
 cooling the autoclave to a room temperature and releasing the hydrogen; 
 adding a protonic acid into the reaction flask for reaction at 80° C. for 6.0 h to obtain a reaction mixture; and 
 subjecting the reaction mixture to neutralizing, washing, extracting and drying to obtain the chiral primary amine. 
 
     
     
       2. The method of  claim 1 , wherein the ketone compound is one of 4-methyl acetophenone, 3-methyl acetophenone, 4-tert-butyl acetophenone, 4-chloroacetophenone, 3-chloroacetophenone, 4-trifluoromethyl acetophenone, 3,4-dichloroacetophenone, 2-acetonaphthone, 1-propiophenone, 6,7,8,9-tetrahydro-5H-benzo[7]cyclopentane-5-one, 1-acetonaphthone and 3-acetylphenylethyl(methyl)carbamate. 
     
     
       3. The method of  claim 1 , wherein the ammonium salt is an ammonium carboxylate salt. 
     
     
       4. The method of  claim 3 , wherein a general formula of the ammonium carboxylate salt is R 3 COONH 4 , wherein R 3  is one of alkyl, cycloalkyl, aryl, aralkyl, alkoxy, cycloalkoxy, aryloxy, aralkoxy and heterocyclyl. 
     
     
       5. The method of  claim 1 , wherein a general formula of the ruthenium-diphosphine catalyst is RuX 2 L; wherein X is one of halogen anions, carboxylate anions, sulfooxy anions, a sulfate radical, a hydrogen sulfate radical, a dihydrogen phosphate radical, a monohydrogen phosphate radical, a phosphite radical, and a nitrate radical; and L is a chiral diphosphine ligand. 
     
     
       6. The method of  claim 1 , wherein the protonic acid is one of hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid and p-toluenesulfonic acid.